Cardiac function as a mechanism for maladaptive brain aging

心脏功能是大脑适应不良老化的机制

基本信息

批准号：
8645566
负责人：
ANGELA L. JEFFERSON
金额：
$ 83.95万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-15 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8645566
关键词：
Adult Affect African American Age Aging Alzheimer&apos s Disease American Animal Model Apolipoprotein E Atherosclerosis Blood Blood Vessels Blood flow Boston Brain Brain Injuries Cardiac Cardiac Output Cardiovascular Diseases Cerebrovascular Circulation Cerebrovascular Disorders Clinical Clinical Research Clinical Sciences Cognitive Complex Data Dementia Development Diabetes Mellitus Diffusion Magnetic Resonance Imaging EFRAC Echocardiography Elderly Epidemiology Executive Dysfunction Functional disorder Funding Future Genetic Grant Hippocampus (Brain)Homeostasis Housing Hypertension Impaired cognition Impairment Incidence Individual Inflammatory Institutes Insulin Resistance Learning Magnetic Resonance Imaging Measurable Mediating Myocardial Myocardial Infarction Neuropsychological Tests Participant Pathway interactions Performance Phenotype Play Population Predisposing Factor Prevalence Prevention strategy Principal Investigator Process Public Health Race Recovery Registries Research Resources Risk Risk Factors Role Testing Time Translational Research Universities Vascular Diseases White Matter Hyperintensity Work age related aging brain bioimaging brain volume central nervous system injury cerebrovascular cognitive change cognitive function design effective therapy executive function inflammatory marker insight mild cognitive impairment neuroimaging neuropsychological novel novel strategies prevent prospective public health relevance research study sex white matter

项目摘要

DESCRIPTION (provided by applicant): As the population continues to age, the incidence of dementia is dramatically increasing, resulting in an urgent need to identify risk factors for abnormal brain aging and dementia. Alterations in cardiac function influence systemic blood flow, which impacts cerebral blood flow homeostasis as demonstrated by animal models. Such changes in cerebral blood flow homeostasis may pose a risk for accelerating age-related brain injury. Our preliminary research suggests that cardiac function is related to markers of maladaptive brain aging. It is not yet clear if cardiac function accelerates neuroimaging or cognitive markers of cerebrovascular or Alzheimer's disease among aging individuals with mild cognitive impairment (MCI). Individuals with MCI are at increased risk for cognitive progression and susceptible to more rapid abnormal brain aging when concomitant vascular disease is present. Our proposed study will examine relations between cardiac function and maladaptive brain aging and provide important information for developing novel strategies to delay the progression from MCI to dementia. Using a prospective observational matched design, we will cross-sectionally and longitudinally relate cardiac function to neuroimaging and cognitive markers of early Alzheimer's disease and cerebrovascular changes among aging adults with MCI and age-, sex-, and race-matched cognitively normal adults. Clinical or subclinical cardiac dysfunction may be due to complex systemic mechanisms that are preventable or treatable, such as enhanced inflammatory markers and insulin resistance, or genetic factors, such as apolipoprotein E. Therefore, we will consider systemic and genetic factors as potential mediating mechanisms in relations between cardiac function and brain aging. The proposed study leverages an existing Alzheimer's Association funded study directed by the principal investigator, the participant registry of our NIA-funded Boston University Alzheimer's Disease Center, a recent American Recovery & Reinvestment Act supplement grant focused on African American recruitment and retention, and the unique resources afforded by our local Clinical and Translational Science Institute housing the General Clinical Research Unit.

描述（由申请人提供）：随着人口的持续年龄，痴呆症的发生率急剧增加，导致迫切需要鉴定出异常的脑衰老和痴呆症的危险因素。心脏功能的改变会影响全身血流，这会影响动物模型所证明的脑血流体内平衡。大脑血流体内平衡的这种变化可能会构成加速与年龄相关的脑损伤的风险。我们的初步研究表明，心脏功能与适应不良的脑衰老的标记有关。目前尚不清楚心脏功能是否会加速患有轻度认知障碍的个体患者（MCI）的脑血管或阿尔茨海默氏病的神经影像或认知标记。患有MCI认知进展的风险增加，并且在存在血管疾病时易受更快的脑老化。我们提出的研究将检查心脏功能与适应不良的大脑衰老之间的关系，并提供重要的信息，以制定新型策略，以延迟MCI的发展。使用前瞻性观察性匹配的设计，我们将在横截面和纵向上将心脏功能与早期阿尔茨海默氏病的神经成像和认知标志物相关联，以及与MCI和年龄，性别，性别，性别 - 性别匹配的认知正常成年人的老年成年人的衰老成年人的脑血管变化。临床或亚临床心脏功能障碍可能是由于可预防或可治疗的复杂的全身机制所致，例如增强的炎症标记和胰岛素抵抗，或遗传因素，例如载脂蛋白E。拟议的研究利用了由主要研究者，我们NIA资助的波士顿大学阿尔茨海默氏病的参与者注册表指导的现有阿尔茨海默氏症协会的资助研究，这是美国近期的美国康复与重新投资法案补充赠款，重点介绍了非裔美国人的招聘和保留，以及我们当地的临床临床研究所的独特资源。